Question

Compare the principles of operation, advantages, and disadvantages of the QIT and the ICR. How are they used in MSn experiments?

QIT = Quadrpole ion trap

ICR = ion cyclotron resonance

Answer 1

Quadrupole Ion Traps

1. Principal of Operation

Ions are dynamically stored in a three-dimensional quadrupole ion storage device. The RF and DC potentials can be scanned to eject successive mass-to-charge ratios from the trap into the de-tector (mass-selective ejection). The theory of the ion trap is beyond the scope of this essay, and the reader is again referred to R. E. March, R. J. Hughes and J. F. Todd, "Quadrupole Storage Mass Spectrometry", volume 102 of Chemical Analysis,Wiley, 1989 for a good description of the theory behind both quadrupole mass filters and quadrupole ion traps.

Ions are formed within the ion trap or injected into an ion trap from an external source. The ions are dynamically trapped by the applied RF potentials (a common trap design also makes use of a "bath gas" to help contain the ions in the trap). The trapped ions can be manipulated by RF events analogous to the events in FTICR to perform ion ejection, ion excitation, and mass-selective ejection. This provides MS/MS and MS/MS/MS... experiments analogous to those per-formed in FTICR.

Space-charge effects (ion-ion repulsion) severly limit the inherent dynamic range of the ion trap. This is usually handled by auto-ranging. That is, a pre-scan is performed to determine the ion current, and then the ionizing electron current is adjusted to reduce the number of ions formed to within the working range. This can be done wherever the ion formation event can be manipulated to control the number of ions formed (such as in electron ionization).

The ions contained within the ion trap can react with any neutral species present. "Self-CI" refers to the case when analyte ions react with analyte neutrals within the trap, and this can produce concentration-dependent changes in the mass spectrum. Such effects can be reduced by injecting ions into the trap from an external source, but ion transmission and trapping losses can lead to reduced sensitivity compared to ion traps that form ions within the trap.

Researchers have demonstrated high resolution and high mass range in specially designed ion trap systems. However, these extended capabilities have not been made generally available in commercial ion trap systems.

2. Benefits

.      High sensitivity

.      Multi-stage mass spectrometry (analogous to FTICR experiments)

.      Compact mass analyzer

3. Limitations

.      Poor quantitation

.      Very poor dynamic range (can sometimes be compensated for by using auto-ranging)

.      Subject to space charge effects and ion molecule reactions

.      Collision energy not well-defined in CID MS/MS

.      Many parameters (excitation, trapping, detection conditions) comprise the experiment sequence that defines the quality of the mass spectrum.

Ion Cyclotron Resonance

1. Principal of Operation

Ions move in a circular path in a magnetic field. The cyclotron frequency of the ion's circular mo-tion is mass-dependent. By measuring the cyclotron frequency, one can determine an ion's mass.

The working equation for ICR can be quickly derived by equating the centripetal force (mv^2/r)

and the Lorentz force evB experienced by an ion in a magnetic field:

Solving for the angular frequency (omega), which is equal to v/r :

A group of ions of the same mass-to-charge ratio will have the same cyclotron frequency, but they will be moving independently and out-of-phase at roughly thermal energies. If an excitation pulse is applied at the cyclotron frequency, the "resonant" ions will absorb energy and be brought into phase with the excitation pulse. As ions absorb energy,the size of their orbit also increases.

The packet of ions passes close to the receiver plates in the ICR cell and induces image currents that can be amplified and digitized. The signal induced in the receiver plates depends on the number of ions and their distance from the receiver plates.

If several different masses are present, then one must apply an excitation pulse that contains components at all of the cyclotron frequencies. This is done by using a rapid frequency sweep ("chirp"), an "impulse" excitation, or a tailored waveform. The image currents induced in the re-ceiver plates will contain frequency components from all of the mass-to-charge ratios. The vari-ous frequencies and their relative abundances can be extracted mathematically by using a Fou-rier transform which converts a time-domain signal (the image currents) to a frequency-domain spectrum (the mass spectrum).

A schematic representation of a cubic FTICR cell is shown below:

The cubic ICR cell consists of three pairs of parallel plates. The functions of the excitation and receiver plates are apparent from the preceding discussion. A small potential is applied to the trapping plates to keep the ions contained within the ICR cell because the magnetic field does not constrain the ion motion along the direction of the applied magnetic field. Beside the cubic cell, many other ICR cell designs have been evaluated, and each has its own special characteristics.

Excitation events can be used to increase the kinetic energy of ions, or to eject ions of a given mass-to-charge ratio from the cell by increasing the orbital radius until ions are lost by collisions with the cell plates.

The background pressure of an FTICR should be very low to minimize ion-molecule reactions and ion-neutral collisions that damp the coherent ion motion. A variety of external ion source

designs have been developed to deal with this problem, and each design has its own performance characteristics.

Most FTICR mass spectrometers use superconducting magnets, which provide a relatively stable calibration over a long period of time. Although some mass accuracy can be obtained without internal calibrant, mass accuracy and resolution are inversely proportional to m/z, and the best accuracte mass measurements require an internal calibrant.

Unlike the quadrupole ion trap, the FTICR mass spectrometer is not operated as a scanning device.

2. Benefits

.      The highest recorded mass resolution of all mass spectrometers

.      Powerful capabilities for ion chemistry and MS/MS experiments

.      Well-suited for use with pulsed ionization methods such as MALDI

.      Non-destructive ion detection; ion remeasurement

.      Stable mass calibration in superconducting magnet FTICR systems

3. Limitations

.      Limited dynamic range

.      Strict low-pressure requirements mandate an external source for most analytical applications

.      Subject to space charge effects and ion molecule reactions

.      Artifacts such as harmonics and sidebands are present in the mass spectra

.      Many parameters (excitation, trapping, detection conditions) comprise the experiment sequence that defines the quality of the mass spectrum

.      Generally low-energy CID, spectrum depends on collision energy, collision gas, and other parameters

Applications of QIT and ICR in MSn Experiments:

For QIT -

In an ion trap mass spectrometer, MS/MS is achieved by the use of an additional sequence of operations in the scan function. The scan function begins with ionization and is followed by selection of a parent ion in a step that involves ejecting all other ions from the trap. The parent ion is then translationally excited, typically by applying a supplementary rf voltage to the end caps. The product ions resulting from collision-induced dissociation of these excited ions with the helium buffer gas are recorded by scanning the rf voltage to perform a second mass-analysis scan. The main advantage of the MS/MS experiment is its enhanced specificity. This is useful in isomer distinction, sequencing of biopolymers, and most particularly in the analysis of complex mixtures. Tandem mass spectrometry experiments eliminate or greatly reduce signals due to other matrix components or instrumental background (chemical noise). A unique feature of the ion trap is the MSn capability which has unprecedented power in structural elucidation. The selectivity of MSn means that a compound can be fragmented, and the resulting fragments further isolated and analyzed to yield structural information about complex molecules in the presence of mixtures

For ICR- (image taken from internet)

The figure shows a schematic of MSⁿ. In the first stage, the normal mass spectrum is produced in the usual way. The isolation of the precursor ion is then performed. In MS/MS, the experiment would end here as the product ions are consumed by the detector; in MSⁿ though, the product ions are trapped allowing another isolation and fragmentation to be performed resulting in the MS³ spectrum. This process can be repeated a number of times, resulting is a series of MSⁿ spectra where 'n' represents the number of times the isolation-fragmentation-measurement cycle has been performed.